An ivermectin – atorvastatin combination impairs nuclear transport inhibiting dengue infection in vitro and in vivo
Selvin Noé Palacios-Rápalo, Carlos Noe Farfán-Morales, Carlos Daniel Cordero‐Rivera, Luis Adrián De Jesús‐González, José Manuel Reyes-Ruíz, Marco Antonio Meraz‐Ríos, Rosa María Del Ángel
Abstract
Dengue virus (DENV) uses cellular nuclear transport machinery to import some proteins into the nucleus. Recently, the non-structural protein 3 (NS3) of DENV was localized in the nucleus of infected cells; however, its nuclear import mechanism is still unknown. In this study, we demonstrate that Ivermectin (IVM) inhibits the nuclear localization of NS3 through the inhibition of the Importin α/β1 pathway. We also report that Atorvastatin (ATV) can modulate the nuclear transport of NS3 protease and NS5 polymerase of DENV-2. On the other hand, we found that IVM and ATV treatments reduce the alteration of nuclear pore complex (NPC) proteins, and an IVM+ATV combination reduced DENV infection both in vitro and in vivo . Hence, we conclude that ATV transport inhibition is an additional antiviral effect of this drug, suggesting a potential anti-DENV therapy in combination with IVM.